1. Proposed sites of action of current multiple sclerosis (MS) treatments
Proposed sites of action of current multiple sclerosis (MS) treatments. In peripheral lymphoid tissues (eg, lymph nodes), autoreactive T cells interact with antigen-presenting cells (APC) and B cells, become activated, and cross the blood–brain barrier. In the CNS, the autoreactive T cells recognize their specific targets and produce effector cytokines, which lead to demyelination and axonal loss. Demyelination and axonal loss are also mediated by macrophages and antibodies (Y shapes). The figure depicts how drugs used to treat MS disrupt this pathologic process. In the periphery, fingolimod blocks T-cell egress from lymph nodes. Alemtuzumab and daclizumab target T and NK cells, while rituximab destroys B cells. Natalizumab blocks T-cell crossing of the blood–brain barrier, while teriflunomide interferes with T-cell proliferation. Interferons and glatiramer alter the process of antigen presentation in the periphery and in the central nervous system (CNS). Also in the CNS, laquinimod is hypothesized to block Th17 cell function, while fumaric acid has several speculative mechanisms of action. Fingolimod might interfere with immune reactions in the CNS in addition to its action in the periphery. Interactions of immune cells and transmigration across the blood–brain barrier are shown with black arrows. Red arrows indicate therapeutic interactions with pointed arrows standing for targeting of specific cell types or molecules, while red lines with a cross-hatch indicate blocking of pathways or receptors. APC, antigen-presenting cell; B, B cell; IL, interleukin; IFN-γ, interferon-γ; NK, natural killer cell; NO, nitric oxide; PC, plasma cell; S1P-R, sphingosine-1-phosphate receptor; Th, T helper cell; TNF-α, tumor necrosis factor-α; VCAM1, vascular cell adhesion molecule 1. (Reproduced with permission from Linker FA, Kieseier BC, Gold R. Identification and development of new therapeutics for multiple sclerosis. Trends Pharmacol Sci. 2008;Nov;29(11):558–565.)
Source: Neuroinflammation, Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e
Citation: Nestler EJ, Hyman SE, Holtzman DM, Malenka RC. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e; 2015 Available at: Accessed: October 19, 2017
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